MicroRNA-221 inhibition in hepatocytes ameliorates liver fibrosis

HC Tsay; Q Yuan; A Balakrishnan; MP Manns; M Ott; A Deep Sharma

doi:10.1055/s-0035-1567972

Zeitschrift für Gastroenterologie, Table of Contents

MicroRNA-221 inhibition in hepatocytes ameliorates liver fibrosis

HC Tsay ¹^,²^,³, Q Yuan ²^,³, A Balakrishnan ²^,³, MP Manns ², M Ott ²^,³, A Deep Sharma ¹^,²

¹Junior Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Hannover, Germany
²Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
³TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany

Abstract

Excessive extracellular matrix accumulation due to chronic liver injury leads to fibrosis, cirrhosis and may then eventually, progress to hepatocellular carcinoma. Small non-coding microRNAs (miRNAs) play important roles in the regulation of multiple liver functions and diseases. Among various miRNAs, miR-221 has recently been reported to be upregulated in liver fibrosis, and its expression correlates with severity of liver fibrosis in HCV patients. We show that downregulation of miR-221 in hepatocytes can ameliorate liver fibrosis by decreasing the activation of HSCs. We inhibited miR-221 expression by an adeno-associated virus encoding a tough decoy against miR-221 (AAV TuD). Reduced levels of serum transaminases and hepatic fibrotic markers were found in mice injected with AAV TuD. Therefore, our findings indicate that suppression of miR-221 in hepatocytes ameliorates liver fibrosis. Our study provides a novel therapeutic approach for the treatment of liver fibrosis via miRNA modulation.

Corresponding author: Sharma, Amar Deep

E-Mail: sharma.amar@mh-hannover.de